How well a tumour responds to immunotherapy may depend in part on whether its chromosomes are intact or in a state of disarray, a new study in Science reports.

The finding could help doctors better pinpoint which cancer patients would benefit from immunotherapy. 

Cancer immunotherapy can produce durable clinical responses, but only in a subset of patients.

Why certain patients benefit more than others is still unclear.

Many tumours are characterised by "aneuploidy," meaning they display an abnormal number of chromosomes and chromosomal segments.

A high degree of aneuploidy is a feature of high-grade tumours and is associated with poor prognosis.

Here, Teresa Davoli and colleagues examined data from over 5,000 tumour samples representing 12 cancer types from The Cancer Genome Atlas (TCGA) project.

The team found that high-aneuploidy tumours had increased expression of genes implicated in DNA replication, cell cycle, mitosis, and chromosome maintenance, yet decreased expression of genes characteristic of the infiltrating immune cells responsible for tumour destruction.

In a retrospective analysis of clinical trial data, they found that melanoma patients with highly aneuploid tumours were less likely to benefit from immune checkpoint blockade therapy than patients whose tumours showed fewer chromosomal disruptions.

Source: Science